The first enzymes of urea biosynthesis, carbamyl phosphate synthase I and ornithine transcarbamylase, will be isolated from rat liver and will be characterized with respect to their physicochemical properties, molecular organization and multiple forms. A systematic approach based on the structure of the enzymes, free of possible effectors or modifying proteins, will establish a basic frame work on which to interpret kinetic behavior, substrate-binding, and interaction with metabolites in order to identify those factors which influence their in vitro activity. The role of N-acetyl-L-glutamate as a key factor in this process will be explored, both in terms of its mechanism of action in the activation of carbamyl phosphate synthetase, as well as its biosynthesis and breakdown. BIBLIOGRAPHIC REFERENCE: Carol J. Lusty (1976). Isolation and Properties of Carbamyl Phosphate Synthetase I from Rat Liver Mitochondria. Fifth Arginine Regulation Workshop, Vrije Universiteit te Brussel, Brussels, Belgium (Abstract).